Xeomin (incobotulinumtoxinA) - 5 indications

Scroll down for additional information on each indication:

• for the treatment of cervical dystonia; approved July 2010
• for the temporary improvement in the appearance of moderate to severe glabellar lines in adults; approved July 2011
• for the treatment of upper limb spasticity in adults; approved December 2015 and expanded August 2020 to include patients 2 years of age and older
• for the treatment of chronic sialorrhea, or excessive drooling, in adults; approved July 2018 and expanded December 2020 to include patients aged 2 years and older
• for the first-line treatment of blepharospasm (involuntary blinking) in adults; approved May 2019

General Information

Xeomin is a Clostridium botulinum type - A neurotoxin complex. Clostridium botulinum toxin type A is a bacterial toxin that prevents nerves from functioning normally (a neurotoxin). It prevents nerves from releasing a chemical called acetylcholine, which is essential for the nerves to communicate with muscle cells. This toxin therefore prevents muscles from receiving nerve stimulation. Botulinum toxin type A causes muscle paralysis until such time as the nerve develops new endings to communicate with the muscles. This it is useful for treating conditions where excessive nerve stimulation to muscles is causing abnormal muscle functioning or spasms.

Xeomin is specifically indicated for the following:

• the treatment of cervical dystonia and blepharospasm
• the temporary improvement in the appearance of moderate to severe glabellar lines in adults
• the treatment of upper limb spasticity in patients 2 years of age and older
• the treatment of chronic sialorrhea, or excessive drooling, in patients aged 2 years and older with chronic sialorrhea, or drooling
• the first-line treatment of blepharospasm (involuntary blinking) in adults

Xeomin is supplied as a solution for intramuscular or intraglandular use. Scroll down for the recommended dosing/administration for each indication.

Mechanism of Action

Xeomin blocks cholinergic transmission at the neuromuscular junction by inhibiting the release of acetylcholine from peripheral cholinergic nerve endings. This inhibition occurs according to the following sequence: neurotoxin binding to cholinergic nerve terminals, internalization of the neurotoxin into the nerve terminal, translocation of the light-chain part of the molecule into the cytosol of the nerve terminal, and enzymatic cleavage of SNAP25, a presynaptic target protein essential for the release of acetylcholine. Impulse transmission is re-established by the formation of new nerve endings.

Side Effects

Adverse events associated with the use of Xeomin for cervical dystonia may include, but are not limited to, the following:

• Dysphagia
• Neck pain
• Muscle weakness
• Injection site pain
• Musculoskeletal pain

Adverse events associated with the use of Xeomin for blepharospasm may include, but are not limited to, the following:

• Eyelid ptosis
• Dry eye
• Dry mouth
• Diarrhea
• Headache
• Visual impairment
• Dyspnea
• Nasopharyngitis
• Respiratory tract infection

Adverse events associated with the use of Xeomin for chronic sialorrhea may include, but are not limited to, the following:

• Chronic Sialorrhea in Adults (≥4% of patients): tooth extraction, dry mouth, diarrhea, and hypertension
• Chronic Sialorrhea in Pediatric Patients (≥1% of patients): bronchitis, headache, and nausea/vomiting 

Adverse events associated with the use of Xeomin for spasticity may include, but are not limited to, the following:

• Upper Limb Spasticity in Adults (≥2% of patients): seizure, nasopharyngitis, dry mouth, and upper respiratory tract infection
• Upper Limb Spasticity in Pediatric Patients (≥3% of patients): nasopharyngitis and bronchitis 

Adverse events associated with the use of Xeomin for glabellar lines may include, but are not limited to, the following: headache

The Xeomin drug label comes with the following Black Box Warning: The effects of Xeomin and all botulinum toxin products may spread from the area of injection to produce symptoms consistent with botulinum toxin effects. These symptoms have been reported hours to weeks after injection. Swallowing and breathing difficulties can be life threatening and there have been reports of death. The risk of symptoms is probably greatest in children treated for spasticity but symptoms can also occur in adults, particularly in those patients who have underlying conditions that would predispose them to these symptoms. 

Indication 1 - for the treatment of cervical dystonia

approved July 2010

Dosing/Administration

Cervical dystonia: the optimum dose, frequency, and number of injection sites in the treated muscle(s) should be based on severity and prior treatment response; individualize dosing for each patient:

• the recommended initial total dose is 120 Units per treatment session 

Clinical Trial Results

A randomized, double-blind, placebo-controlled, multi-center phase III trial enrolled 233 patients with cervical dystonia. The baseline Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total score ≥20, TWSTRS severity score ≥10, TWSTRS disability score ≥3, and TWSTRS pain score ≥1. The subjects received a single administration of Xeomin 240 Units (n=81), Xeomin 120 Units (n=78), or placebo (n=74). The investigator at each site decided which muscles would receive injections of Xeomin, the number of injection sites, and the volume at each site. The primary efficacy endpoint was the change in the TWSTRS total score from baseline to Week 4 post-injection. In the ITT population, the difference between the Xeomin 240 Unit group and the placebo group in the change of the TWSTRS total score from baseline to Week 4 was -9.0 points; the difference between the Xeomin 120 Unit group and the placebo group in the change of the TWSTRS total score from baseline to Week 4 was -7.5 points. Both results were statistically significant over placebo.

Indication 2 - for the temporary improvement in the appearance of moderate to severe glabellar lines in adults

approved July 2011

Dosing/Administration

The recommended dose is 20 Units per treatment session, divided into five equal intramuscular injections of 4 Units each (two injections in each corrugator muscle and one injection in the procerus muscle; wait a minimum of three months before retreatment. 

Clinical Trial Results

Two identically designed randomized, double-blind, multi-center, placebo controlled clinical trials (Studies GL-1 and GL-2) were conducted to evaluate Xeomin for use in the temporary improvement of moderate to severe glabellar lines. The studies enrolled 547 healthy patients (≥18 years old) with glabellar lines of at least moderate severity at maximum frown. Three hundred sixty six subjects were treated with 20 Units of Xeomin and 181 subjects were treated with placebo. Subjects were followed up for 120 days. Investigators and subjects assessed efficacy at maximum frown on Day 30 of treatment using a 4-point scale (0=none, 1=mild, 2=moderate, 3=severe). Composite treatment success was defined as a 2-grade improvement on this scale compared to baseline for both the investigator's and subject's assessments on Day 30. The percentage of subjects with treatment success was greater on the XEOMIN arm than the placebo arm at Day 30 in both studies. Composite treatment success in Study 1 was 68% versus 0% and Study 2: 48% versus 0% for Xeomin versus placebo, respectively.

Indication 3 - for the treatment of upper limb spasticity in patients 2 years of age and older

approved December 2015, August 2020

Dosing/Administration

Upper limb spasticity: the optimum dose, frequency, and number of injection sites in the treated muscle(s) should be based on severity and prior treatment response; individualize dosing for each patient:

• Upper Limb Spasticity in Adults: the recommended total dose is up to 400 Units, divided among affected muscles 
• Upper Limb Spasticity in Pediatric Patients, excluding spasticity caused by cerebral palsy: the recommended total dose is 8 Units/kg (maximum 200 Units) per single upper limb or 16 Units/kg (maximum 400 U) in both upper limbs, divided among affected muscles 

Clinical Trial Results

The FDA approval for adults was based on results of a randomized, multicenter, placebo-controlled trial showing significant improvements in two co-primary outcome parameters: muscle tone (Ashworth Scale score) and the Investigator’s Global Impression of Change of the Primary Target Clinical Pattern (PTCP) at Week 4. Both showed statistical significance, with p < 0.001 and p = 0.003 respectively. The trial also met a key secondary outcome measure, in which subjects with an improvement ≥1 on the Ashworth Scale at Week 4 were classified as responders.

The FDA approval for pediatrics was based on a Phase 3 study of 350 patients aged 2 to 17 years that looked at the safety and efficacy of incobotulinumtoxinA. Primary efficacy endpoints were changed from baseline on the 5-point Ashworth Scene and a 7-point Investigator’s Global Impression of Change Scale at the fourth week of treatment. The study illustrated sustained improvement in muscle tone in all upper limb muscle groups including flexed elbow, flexed wrist, forearm pronators, clenched fist, and thumb-in-palm. 

Indication 4- for the treatment of chronic sialorrhea, or excessive drooling, in patients 2 years of age and older

Approved July 2018, December 2020

Dosing/Administration

• Chronic Sialorrhea in Adults: the recommended total dose is 100 Units per treatment session consisting of 30 Units per parotid gland and 20 Units per submandibular gland, no sooner than every 16 weeks
• Chronic Sialorrhea in Pediatric Patients: the recommended dose is based on body weight administered in a 3:2 dose ratio into the parotid and submandibular glands, respectively, no sooner than every 16 weeks; ultrasound guidance recommended 

Clinical Trial Results

FDA approval in adults was based on results from the randomized, double-blind, placebo-controlled Phase 3 SIAXI clinical trial. The trial enrolled a total of 184 adults with excessive drooling associated with Parkinson's disease, stroke, or traumatic brain injury who received either 75 Units (U) or 100 U of Xeomin or a placebo. The effectiveness and safety of Xeomin was compared to placebo in reducing the salivary flow rate, and the severity and frequency of chronic sialorrhea. Compared with pre-treatment assessments and with placebo, 100 U of Xeomin significantly reduced the unstimulated salivary flow rate (uSFR) and the severity and frequency of excessive drooling — as assessed by the Global Impression of Change Scale (GICS), routinely used in studies of neurological disorders — at four weeks.

FDA approval for pediatrics was based on a phase 3 prospective, randomized, double-blind, placebo-controlled, multicenter study evaluating the safety and efficacy of Xeomin in 255 children and adolescents aged 2 to 17 years. Xeomin demonstrated significantly reduced unstimulated salivary flow rate and functional improvement in drooling versus placebo among patients aged 6 ‒ 17 years after four weeks, and sustained efficacy over 64 weeks. Patients aged 2 to 5 also showed comparably improved function. No patients demonstrated clinical resistance or secondary treatment failure due to neutralizing antibodies.

Indication 5 - for the first-line treatment of blepharospasm (involuntary blinking) in adults

approved May 2019

Dosing/Administration

Blepharospasm: the optimum dose, frequency, and number of injection sites in the treated muscle(s) should be based on severity and prior treatment response; individualize dosing for each patient:

• the recommended initial total dose is 50 Units (25 Units per eye) 

Clinical Trial Results

A randomized, double-blind, placebo-controlled, multi-center phase III trial enrolled 109 patients with blepharospasm. The baseline Jankovic Rating Scale (JRS) Severity subscore ≥2, and a stable satisfactory therapeutic response to previous administrations of onabotulinumtoxinA (Botox). At least 10 weeks had to have elapsed since the most recent onabotulinumtoxinA administration. The subjects were randomized to receive a single administration of Xeomin or placebo. The Xeomin treatment (dose, volume, dilution, and injection sites per muscle) that was similar to the most recent onabotulinumtoxinA injection sessions prior to study entry. The highest dose permitted in this study was 50 Units per eye; the mean Xeomin dose was 33 Units per eye. The primary efficacy endpoint was the change in the JRS Severity subscore from baseline to Week 6 post-injection. The difference between the Xeomin arm and the placebo arm in the change of the JRS Severity subscore from baseline to Week 6 was -1.0.